Treatment of psoriasis with topical sirolimus

preclinical development and a randomized, double-blind trial

Anthony Ormerod, S.A.A. Shah, P Copeland, G Omar, A Winfield

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

BACKGROUND: Systemically administered sirolimus has demonstrated efficacy in psoriasis in a multicentre European study. OBJECTIVES: To determine the efficacy and safety of topically applied sirolimus in treating psoriasis. METHODS: In vitro studies were followed by a pilot study designed to determine if sirolimus penetrates human skin, and by a randomized, double-blind, left-right comparative, dose-ranging study consisting of treatment with 2.2% sirolimus for 6 weeks and 8% sirolimus for an additional 6 weeks in 24 patients with stable, chronic plaque psoriasis. The primary outcome measure was clinical score. Secondary measures were ultrasound plaque thickness, plaque erythema, and computerized image analysis of immunohistochemical stains for immunocytes and proliferating cells. Pharmacokinetics and blood chemistry monitoring for safety were also performed. RESULTS: A significant reduction in the clinical score (P = 0.03) (mean score 9.1 following sirolimus vs. 11.2 in control) was achieved with topical sirolimus. Measurements of plaque thickness and erythema did not show significant improvement with treatment. Computerized image analysis of biopsies showed a significant reduction in CD4+ cells (P = 0.0054) and proliferating cells (stained by Ki-67) in the epidermis (P = 0.0153) with sirolimus treatment compared with control. CONCLUSIONS: Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.
Original languageEnglish
Pages (from-to)758-764
Number of pages7
JournalBritish Journal of Dermatology
Volume152
Issue number4
Early online date24 Mar 2005
DOIs
Publication statusPublished - 1 Apr 2005

Keywords

  • Administration, Topical
  • Adult
  • Aged
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunohistochemistry
  • Immunosuppressive Agents
  • Male
  • Middle Aged
  • Pilot Projects
  • Psoriasis
  • Sirolimus
  • Skin
  • Treatment Outcome
  • Immunosuppressant
  • Randomized controlled trial
  • Therapy
  • Topical
  • Assay
  • Immunosuppressant
  • Pyoderma-Gangrenosum
  • Tacrolimus Ointment
  • Atopic dermatitis
  • Cyclosporine-A
  • Rapamycin
  • Reduction
  • Efficacy
  • Lesions

Cite this

Treatment of psoriasis with topical sirolimus : preclinical development and a randomized, double-blind trial. / Ormerod, Anthony; Shah, S.A.A.; Copeland, P; Omar, G; Winfield, A.

In: British Journal of Dermatology, Vol. 152, No. 4, 01.04.2005, p. 758-764.

Research output: Contribution to journalArticle

Ormerod, Anthony ; Shah, S.A.A. ; Copeland, P ; Omar, G ; Winfield, A. / Treatment of psoriasis with topical sirolimus : preclinical development and a randomized, double-blind trial. In: British Journal of Dermatology. 2005 ; Vol. 152, No. 4. pp. 758-764.
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abstract = "BACKGROUND: Systemically administered sirolimus has demonstrated efficacy in psoriasis in a multicentre European study. OBJECTIVES: To determine the efficacy and safety of topically applied sirolimus in treating psoriasis. METHODS: In vitro studies were followed by a pilot study designed to determine if sirolimus penetrates human skin, and by a randomized, double-blind, left-right comparative, dose-ranging study consisting of treatment with 2.2{\%} sirolimus for 6 weeks and 8{\%} sirolimus for an additional 6 weeks in 24 patients with stable, chronic plaque psoriasis. The primary outcome measure was clinical score. Secondary measures were ultrasound plaque thickness, plaque erythema, and computerized image analysis of immunohistochemical stains for immunocytes and proliferating cells. Pharmacokinetics and blood chemistry monitoring for safety were also performed. RESULTS: A significant reduction in the clinical score (P = 0.03) (mean score 9.1 following sirolimus vs. 11.2 in control) was achieved with topical sirolimus. Measurements of plaque thickness and erythema did not show significant improvement with treatment. Computerized image analysis of biopsies showed a significant reduction in CD4+ cells (P = 0.0054) and proliferating cells (stained by Ki-67) in the epidermis (P = 0.0153) with sirolimus treatment compared with control. CONCLUSIONS: Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.",
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T1 - Treatment of psoriasis with topical sirolimus

T2 - preclinical development and a randomized, double-blind trial

AU - Ormerod, Anthony

AU - Shah, S.A.A.

AU - Copeland, P

AU - Omar, G

AU - Winfield, A

PY - 2005/4/1

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N2 - BACKGROUND: Systemically administered sirolimus has demonstrated efficacy in psoriasis in a multicentre European study. OBJECTIVES: To determine the efficacy and safety of topically applied sirolimus in treating psoriasis. METHODS: In vitro studies were followed by a pilot study designed to determine if sirolimus penetrates human skin, and by a randomized, double-blind, left-right comparative, dose-ranging study consisting of treatment with 2.2% sirolimus for 6 weeks and 8% sirolimus for an additional 6 weeks in 24 patients with stable, chronic plaque psoriasis. The primary outcome measure was clinical score. Secondary measures were ultrasound plaque thickness, plaque erythema, and computerized image analysis of immunohistochemical stains for immunocytes and proliferating cells. Pharmacokinetics and blood chemistry monitoring for safety were also performed. RESULTS: A significant reduction in the clinical score (P = 0.03) (mean score 9.1 following sirolimus vs. 11.2 in control) was achieved with topical sirolimus. Measurements of plaque thickness and erythema did not show significant improvement with treatment. Computerized image analysis of biopsies showed a significant reduction in CD4+ cells (P = 0.0054) and proliferating cells (stained by Ki-67) in the epidermis (P = 0.0153) with sirolimus treatment compared with control. CONCLUSIONS: Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.

AB - BACKGROUND: Systemically administered sirolimus has demonstrated efficacy in psoriasis in a multicentre European study. OBJECTIVES: To determine the efficacy and safety of topically applied sirolimus in treating psoriasis. METHODS: In vitro studies were followed by a pilot study designed to determine if sirolimus penetrates human skin, and by a randomized, double-blind, left-right comparative, dose-ranging study consisting of treatment with 2.2% sirolimus for 6 weeks and 8% sirolimus for an additional 6 weeks in 24 patients with stable, chronic plaque psoriasis. The primary outcome measure was clinical score. Secondary measures were ultrasound plaque thickness, plaque erythema, and computerized image analysis of immunohistochemical stains for immunocytes and proliferating cells. Pharmacokinetics and blood chemistry monitoring for safety were also performed. RESULTS: A significant reduction in the clinical score (P = 0.03) (mean score 9.1 following sirolimus vs. 11.2 in control) was achieved with topical sirolimus. Measurements of plaque thickness and erythema did not show significant improvement with treatment. Computerized image analysis of biopsies showed a significant reduction in CD4+ cells (P = 0.0054) and proliferating cells (stained by Ki-67) in the epidermis (P = 0.0153) with sirolimus treatment compared with control. CONCLUSIONS: Topically applied sirolimus penetrates normal skin and may have some antipsoriatic and immunosuppressive activity.

KW - Administration, Topical

KW - Adult

KW - Aged

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Female

KW - Humans

KW - Immunohistochemistry

KW - Immunosuppressive Agents

KW - Male

KW - Middle Aged

KW - Pilot Projects

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KW - Assay

KW - Immunosuppressant

KW - Pyoderma-Gangrenosum

KW - Tacrolimus Ointment

KW - Atopic dermatitis

KW - Cyclosporine-A

KW - Rapamycin

KW - Reduction

KW - Efficacy

KW - Lesions

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DO - 10.1111/j.1365-2133.2005.06438.x

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SP - 758

EP - 764

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

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ER -